Influence of substitution on kinetics and mechanism of ring transformation of substituted S-[1-phenylpyrrolidin-2-on-3-yl]isothiuronium salts

Abstract

Twelve new substituted S-(1-phenylpyrrolidin-2-on-3-yl)isothiuronium bromides and twelve corresponding 2-imino-5-(2-phenylaminoethyl)thiazolidin-4-ones have been prepared and characterised. Kinetics and mechanism of transformation reaction of S-[1-(4-methoxyphenyl)pyrrolidin-2-on-3-yl]isothiuronium bromide 1a and its N,N-dimethyl derivative 5a into corresponding substituted thiazolidin-4-ones 2a and 6a have been studied in aqueous solutions of amine buffers (pH 8.1–11.5) and sodium hydroxide solutions (0.005–0.5 mol l⁻¹) at 25 °C and at I = 1 mol l⁻¹ under pseudo-first-order reaction conditions. The kinetics observed show that the transformation reaction is subject to general acid–base, and hydroxide ion catalyses. Acid catalysis does not operate in the transformation of 1a; the rate-limiting step of the base-catalysed transformation is the decomposition of bicyclic tetrahedral intermediate In^± and the Brønsted dependence is non-linear (pK_a ≈ 9.8). In the case of derivative 5a both base and acid catalyses make themselves felt. In the base catalysis, the rate-limiting step consists of the decomposition of bicyclic intermediate In, and the Brønsted dependence is linear (β = 0.9; pK_a > 11.5). The acid-catalysed transformation of 5a also proceeds via the intermediate In, and the reaction is controlled by diffusion (α ≈ 0). With compound 5a in triethylamine and butylamine buffers, the general base catalysis changes into specific base catalysis. The effect of substitution in aromatic moiety of compounds 1a–h and 3a–h on the course of the transformation reaction has been studied in solutions of sodium hydroxide (0.005–0.5 mol l⁻¹) at 25 °C by the stopped-flow method. The electron-acceptor substituents 4-NO₂ and 4-CN do not obey the Hammett correlation, which is due to a suppression of cross-conjugation in the ring-closure step of the transformation reaction.